This invention is directed to certain tripeptides and use as anti-depressant and/or thyroid hormone release stimulants-and processes for their preparation.
The naturally occurring thyrotropin releasing hormone (TRH) is the tripeptide L-pyroglutamyl-L-histidyl-L-proline amide. Methods of synthesizing this peptide are known. Specific processes are described in U.S. Pat. Nos. 3,753,569; 3,746,697; 3,757,003, and 3,752,800. Analogs, derivatives and isomers of TRH are also disclosed in "Vitamins and Hormones, Advances in Research and Applications" volume 29 pg. 1-39, Academic Press, N.Y. and London (1971); "Chemistry and Biology of Peptides, Proceedings of the Third American Peptide Symposium" pg. 601-608, Ann Arbor Science Publishers Inc., Ann Arbor, Michigan (1972); Zh. Obshch, Khim 42 No. 2, pg. 483, February (1972); J. Med. Chem. 15, pg. 8, 219, 479 (1972); J. Med. Chem. 16, pg. 1137-1140 (1973); C.A. 75, 49547 w, 49548 x, 77268 z, 88942 r (1971); C. A. 74, 13401 m, (1971); and C. A. 73, 21767 c, 95001 v (1970). Besides its thyroid hormone release stimulating activity, TRH has also been found to have anti-depressant effect of substantially immediate onset. [Prage Jr., et al., LANCET pg. 999, Nov. 11, 1972; Plotnikoff, et al., SCIENCE, 178,417 (1972)].
Novel tripeptides have been prepared having antidepressant activity and thyrotropin hormone release activity of the TRH type.